The present invention relates to liquid dispensing devices. More particularly, the present invention relates to a method and apparatus for providing enhanced control/regulation over the delivery of micro volumes of liquid from such liquid dispensing devices.
Automated dispensing of miro-liter quantities of fluids is required, or at least desirable, in pharmaceutical, combinatorial chemistry, high-throughput screening and medical diagnostic applications. It is difficult, however, to accurately dispense fluids in micro-liter quantities.
In particular, it is very difficult to dispense liquid in an amount in the range of about 0.1-2 micro liters while minimizing cross-contamination between the dispenser and a receiver. To substantially eliminate the incidence of crosscontamination, a xe2x80x9cnon-touch offxe2x80x9d method of fluid delivery is used. In such a method, there should be no contact between a droplet being dispensed and the receiver (or fluid or other material in the receiver) until the droplet completely disengages from the tip of the dispenser. Non-touch-off transfer requires supplying kinetic energy to a droplet in an amount sufficient to overcome the surface tension of the dispensing tip and to dispense the droplet with sufficient momentum that it can be accurately and reliably directed to a desired destination.
Techniques borrowed from the printing industry (e.g., ink jet printers) have been used to create dispensers for dispensing liquid volumes of less than about 100 nano-liters. Such dispensers use piezo, thermal, magnetostrictive and other means of generating micro deformations to displace and supply kinetic energy to nano-liter quantities of fluid. Such methods/apparatuses are limited, however, to dispensing nano-liter volumes of fluid, and are also very sensitive to fluid parameters. These methods and apparatuses are therefore of limited utility for pharmaceutical, combinatorial chemistry, high-throughput screening and medical diagnostic applications wherein the characteristics of the liquids may vary widely from application to application.
Methods/apparatuses capable of non-touch-off transfer of liquid volumes in the range of about 0.1 to about 3 micro-liters include xe2x80x9cshake offxe2x80x9d methods and methods that use valving mechanisms for portioning out a desired volume. Dispensers that incorporate such valving mechanisms have proven to be difficult to implement due to a variety of factors, as discussed below.
Some prior art valve-implemented dispensers utilize a xe2x80x9cpositive-displacementxe2x80x9d method wherein a predetermined portion of fluid is pressurized into the valve while a synchronized valve controller appropriately actuates the valve. See, for example, U.S. Pat. No. 5,741,554. While developed to provide improved precision for the delivery of micro-liter volumes of fluid, the positive-displacement method has a number of shortcomings.
In particular, dispensers utilizing this method depend on precise coordination of all controls, a suitably elastic liquid channel (apparently overlooked in U.S. Pat. No. 5,741,554), and are subject to temperature variations, variations due to entrapped or internally-released gas bubbles, as well as variations in other parameters.
Positive-displacement dispensers also suffer from an unavoidable drop in liquid pressure during each individual dispense cycle caused by the delay between syringe (piston) action and high speed valve operation. This, in turn, results in variations in droplet formation, wherein an insufficient quantity of kinetic energy is available to cause droplet separation during the xe2x80x9cfalling edgexe2x80x9d phase of the droplet-forming pressure pulse.
As such, there is a need for improvements in the liquid dispensers of the prior art.
Flow-control/regulation means for improving a liquid-dispensing operation, and liquid dispensers incorporating the same, are disclosed. In a first embodiment, the flow-regulation means comprises a conduit for receiving a pressurized fluid, wherein said conduit is in fluid communication with a dispensing valve for dispensing the fluid. As used herein, the phrase xe2x80x9cfluid communication,xe2x80x9d indicates that fluid (i.e., liquid and/or gas) can flow directly between two regions (i.e., the two regions that are described to be in fluid communication). Flow is regularly re-supplied to the dispensing valve, so the problem suffered by positive-displacement dispensers concerning the availability of sufficient pressure during the entire dispensing cycle is avoided.
In the first embodiment, a flow restriction restricts the flow of the pressurized liquid into the conduit. The flow restriction, which in some embodiments is realized as a restriction orifice, has an orifice that is smaller than the outlet opening or orifice of the dispensing valve. As a result, liquid is re-supplied to the conduit more slowly than it is dispensed through the dispensing valve. Since the re-supply rate is less than the dispensing rate, a relatively smaller error results from delays in valve closing than would otherwise occur.
In a second embodiment, the flow-regulation means comprises a conduit for receiving liquid to be dispensed, wherein said conduit is in fluid communication with a dispensing valve. In the second embodiment, at least a portion of the conduit is elastic. A dynamic pressure sensor senses pressure in the elastic region. Such pressure can be correlated to the amount of liquid discharged from the dispenser, can provide an indication of operating problems, or can provide corrective control.
In a third embodiment, the flow-regulation means comprises a conduit for receiving liquid to be dispensed, wherein said conduit is in fluid communication with a dispensing valve. Again, at least a portion of the conduit is elastic. In this embodiment, the flow-regulation means also comprises a resilience-adjustment means operable to adjust the resilience or elasticity of the elastic portion of the conduit. Such adjustable resilience provides an additional measure of control over the dispensing process. In particular, the resilience-adjustment means can compensate for changes in fluid characteristics (e.g., viscosity, etc.) as well as for changes in the elasticity of the elastic portion of the conduit or in the mechanical operation of the dispensing valve.
In additional embodiments, a flow-regulation means in accordance with the present teachings comprises various combinations of the features of embodiments one, two and three.